The interaction between virus and host defenses is complex. A defect in transformation-enhancing function of virus-infected human macrophages can account for the depression of lymphocyte transformation response to mitogens that is observed during in vitro influenza virus infection. Concurrently, the infected macrophages produce the antiviral substance interferon. Furthermore, fever of hyperthermia is a common response to infection with viruses, and has been associated with enhanced resistance to viral infection in animal models. The objective of this proposal is to further our understanding of the interaction between viruses and human immune defense mechanisms by determining whether the prior immunologic experience of the leukocyte donor modifies the effects of virus on transformation response and interferon production, uhether the adverse effects of in vitro virus infection are reversible and whether they are related to the infectivity of the virus, whether certain of the effects are mediated by interferon, whether other functions of macrophages are activated by virus or interferon, and whether hyperthermia or interferon enhance macrophage resistance to or recovery from virus infection. Assays of function of human mononuclear leukocytes and highly purified macrophage and lymphocyte preparations (alone or re-combined) for transformation response to mitogen and interferon production will be carried out with control cells and cells exposed to infectious and heat-inactivated virus, with an influenza virus strain familiar and unfamiliar to the leukocyte donors, with and without addition of interferon produced by virus-infected macrophages to the cultures, with varying proportions of control and virus-infected macrophages present in culture, and with variation of temperature of incubation at times prior to and after infection. Sequential assays will determine the time course as well as reversibility of effects. Assays for activation of control, interferon-treated, and virus-infected macrophages will be performed. Interferons produced will be characterized.